Polymer-flavonoid conjugate and uses thereof

Abstract

There is provided a polymer-flavonoid conjugate, or a pharmaceutically acceptable salt thereof, uses thereof, and methods of making thereof. The disclosed polymer-flavonoid conjugates may be useful in the therapeutic and/or prophylactic treatment of a joint condition in a subject.

The invention claimed is: 
     
       1. A method for treating a joint condition in a subject in need thereof comprising administering a therapeutically effective amount of a polysaccharide-flavonoid conjugate to said subject,
 wherein the polysaccharide of said polysaccharide-flavonoid conjugate is conjugated to one or more flavonoids at the C2 and/or C6 position of the B ring of said flavonoid(s), and 
 wherein the joint condition is selected from the group consisting of osteoarthritis, rheumatoid arthritis, gouty arthritis, juvenile arthritis, psoriatic arthritis, and ankylosing spondylitis. 
 
     
     
       2. The method according to  claim 1 , wherein the joint condition is osteoarthritis. 
     
     
       3. The method according to  claim 1 , wherein one or more flavonoids are conjugated to said polysaccharide. 
     
     
       4. The method according to  claim 1 , wherein said polysaccharide is conjugated to said one or more flavonoids via a linker. 
     
     
       5. The method according to  claim 1 , wherein said one or more flavonoids is a monomeric flavonoid or a dimeric flavonoid. 
     
     
       6. The method according to  claim 1 , wherein the polysaccharide is conjugated to the flavonoid via a thiol linker, wherein the thiol linker further comprises a moiety bound to the polysaccharide, wherein said moiety is selected from the group consisting of an amide, an amine, an alkyl, an alkenyl, an aryl, an ester, a carbonate, an ether, an amido, an amido ester, a carbamate and an acetal group. 
     
     
       7. The method according to  claim 1 , wherein the polysaccharide is selected from the group consisting of hyaluronic acid, dextran, cellulose, amylose, starch, gelatin, alginate, chitosan, carrageenan, cyclodextrin, dextran sulfate, Ficoll, gellan, guar gum, pectin, polysucrose, pullulan, scleroglucan, xanthan and xyloglucan. 
     
     
       8. The method according to  claim 1 , wherein the flavonoid is selected from the group consisting of flavones, isoflavones, flavans, proanthocyanidins, anthocyanidins, (−)-epicatechin, (+)-epicatechin, (−)-catechin, (+)-catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, Fisetinidol, Gallocatechin, Gallocatechin gallate, Mesquitol and Robinetinidol, ellagitannin, gallotannin, oolongtheanin, phlorotannin, tannin, theacitrin, theadibenzotropolone, theaflavin, theanaphthoquinone, thearubigins, theasinensin and mixtures thereof. 
     
     
       9. The method according to  claim 1 , the one or more flavonoids is epigallocatechin gallate and wherein the polysaccharide is conjugated to at least one epigallocatechin gallate. 
     
     
       10. The method according to  claim 9 , wherein the polysaccharide is conjugated to at least one epigallocatechin gallate via a thiol linker. 
     
     
       11. The method according to  claim 9 , wherein the polysaccharide is conjugated to at least one epigallocatechin gallate at the C2 and/or C6 ring of the B ring of said epigallocatechin gallate. 
     
     
       12. The method according to  claim 1 , wherein the polysaccharide-flavonoid conjugate is of Formula 1: 
       
         
           
           
               
               
           
         
         wherein: 
         each n is independently an integer from 0 to 50,000 inclusive; and each m is independently an integer from 0 to 50,000 inclusive, wherein at least one of m or n is not 0. 
       
     
     
       13. The method according to  claim 12 , wherein the polysaccharide-flavonoid conjugate of Formula 1 has a degree of conjugation from 0.1 to 50%. 
     
     
       14. The method according to  claim 1 , wherein said therapeutic treatment of the joint condition results in cartilage repair.